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One- versus three-week schedule for adjuvant whole breast radiation therapy in early breast cancer
For patients receiving adjuvant whole breast radiation therapy (WBRT) for early breast cancer, conventional dosage schedules are given over several weeks, while "hypofractionated" schedules complete treatment over a shorter timeframe. In a randomized trial of over 4000 patients with early breast cancer, a hypofractionated schedule (26 Gy in five fractions over one week) reduced the rate of five-year ipsilateral breast tumor relapse compared with a conventional adjuvant schedule (40 Gy over three weeks) (1.4 versus 2.1 percent) [1]. Further study is needed to clarify outcomes in higher-risk subgroups, who may need an additional field to cover the regional lymph nodes. Based on these and previous data, for women with early breast cancer receiving adjuvant WBRT and lacking indications for regional nodal radiation, we suggest a hypofractionated rather than conventional schedule.
Nivolumab for PD-L1-overexpressing biliary tract cancer
Immune checkpoint inhibitors have broad activity against a wide variety of histologic tumor subtypes that have deficient DNA mismatch repair (dMMR), but other biomarkers may also be predictive. In a phase II trial of nivolumab in 46 patients with advanced refractory biliary tract cancer (BTC), 18 of 42 tested tumors (43 percent) overexpressed programmed cell death 1 ligand 1 (PD-L1) [2]. Of the 10 patients achieving an investigator-assessed immune partial response, none had dMMR, but nine overexpressed PD-L1. These data underscore the importance of targeted testing of advanced BTC for specific molecular alterations, including PD-L1 overexpression, for which a targeted treatment might be available.
Long-term survival outcomes for encorafenib and binimetinib in BRAF V600-mutated metastatic melanoma
The combination of BRAF and MEK inhibitors is an established treatment option in patients with metastatic melanoma harboring a BRAF V600 mutation, but long-term data for this combination are limited. In a phase III trial (COLUMBUS) of approximately 600 patients with BRAF V600-mutated melanoma, at median follow-up of approximately four years, the combination of the BRAF inhibitor encorafenib plus the MEK inhibitor binimetinib improved both progression-free (median 15 versus 7 months) and overall (median 34 versus 17 months) survival compared with the single-agent BRAF inhibitor vemurafenib, and the combination remained safe and tolerable [3]. This study confirms the long-term efficacy and safety of encorafenib and binimetinib in patients with BRAF V600-mutated metastatic melanoma, and it remains one of our preferred treatment options in this population.
Paclitaxel for AIDS-related Kaposi sarcoma in resource-limited settings
Patients with treatment-naive AIDS-related Kaposi sarcoma (KS) are preferably treated using liposomal anthracyclines. However, this agent may not be accessible in resource-limited settings. In an open-label randomized trial of approximately 330 patients with treatment-naive KS in Africa and South America, intravenous paclitaxel improved 48-week progression-free survival compared with single-agent oral etoposide (50 versus 20 percent) and bleomycin plus vincristine (64 versus 44 percent) [4]. Time to death was similar among all treatment arms. All patients in the study also received antiretroviral therapy (ART). Based on these results, we offer paclitaxel as initial treatment for patients with AIDS-related KS in resource-limited settings where liposomal anthracyclines are not accessible.
Novel targeted therapies in NSCLC
Novel strategies for treating advanced non-small cell lung cancer (NSCLC) with genetic driver mutations are evolving.
* In preliminary results of a study including nearly 100 patients with advanced NSCLC harboring a MET exon 14 skipping mutation, the response rate to the MET inhibitor capmatinib was 68 percent among treatment-naive patients and 41 percent among those with prior treatment [5]. Toxicities included peripheral edema, nausea and vomiting, and increased creatinine.
* In preliminary results of a separate study of nearly 150 patients with advanced RET fusion-positive NSCLC, the response rate to the RET inhibitor selpercatinib was 85 percent among treatment-naive patients and 64 percent among those who had progressed on prior platinum-based chemotherapy [6]. Severe toxicities included hypertension, prolonged QT interval, diarrhea, and dyspnea.
Based on these data, the US Food and Drug Administration (FDA) has approved capmatinib for advanced NSCLC associated with a MET exon 14 skipping mutation, and selpercatinib for those with advanced RET fusion-positive NSCLC [6,7].
1. Murray Brunt A, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet 2020; epub April 28, 2020.
2. Kim RD, Chung V, Alese OB, et al. A Phase 2 Multi-institutional Study of Nivolumab for Patients With Advanced Refractory Biliary Tract Cancer. JAMA Oncol 2020.
3. Ascierto PA, Dummer R, Gogas HJ, et al. Update on tolerability and overall survival in COLUMBUS: landmark analysis of a randomised phase 3 trial of encorafenib plus binimetinib vs vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. Eur J Cancer 2020; 126:33.
4. Krown SE, Moser CB, MacPhail P, et al. Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial. Lancet 2020; 395:1195.
5. Garon EB, Heist RS, Seto T, et al. CT082 - Capmatinib in METex14-mutated (mut) advanced non-small cell lung cancer (NSCLC): Results from the phase II GEOMETRY mono-1 study, including efficacy in patients (pts) with brain metastases (BM). AACR April 2020.
6. Selpercatinib capsules, for oral use. United States Prescribing Information. US National Library of Medicine. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213246s000lbl.pdf (Accessed on May 11, 2020).
7. Capmatinib tablets, for oral use. United States Prescribing Information. US National Library of Medicine. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213591s000lbl.pdf (Accessed on May 07, 2020).
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